Terminé

A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)

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Ce qui est testé

Azacitidine

+ Physician Choice
Médicament
Autre
Qui peut participer

Maladies de la moelle osseuse
+6

+ Maladie
+ Maladies Hématologiques
À partir de 18 ans
Voir tous les critères d'éligibilité
Comment se déroule l'étude

Autre étude

Phase 3
Interventionnel
Date de début : novembre 2003
Voir le détail du protocole

Résumé

Sponsor principalCelgene
Dernière mise à jour : 14 janvier 2026
Issu d'une base de données validée par les autorités. Revendiquer cette étude
Date de début de l'étude : 1 novembre 2003Date à laquelle le premier participant a commencé l'étude.

Comparison/Control Interventions offered the physician three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care. Neither the experimental group (azacitidine) nor any of the comparison/control options allowed use of erythropoietin. Duration of Intervention: Patients will be treated until death, withdrawal, unacceptable toxicity or conclusion of the study.

Titre officielA Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS) 
NCT00071799
Sponsor principalCelgene
Dernière mise à jour : 14 janvier 2026
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Protocole

Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.
Détails du design
358 participants à inclureNombre total de participants que l'essai clinique vise à recruter.
Autre
Cette catégorie concerne les études qui ne relèvent d'aucune des catégories précédentes. Cela peut inclure des recherches innovantes, de nouvelles technologies ou des domaines émergents de la santé.

Comment les participants sont répartis entre les groupes de l'étude
Dans cette étude clinique, les participants sont répartis de manière aléatoire, comme lors d'un tirage au sort. Cela garantit l'équité et réduit les biais, rendant les résultats plus fiables. En attribuant les participants au hasard, les chercheurs peuvent comparer les traitements sans influence extérieure.

Autres méthodes de répartition
Répartition non aléatoire : basée sur des critères spécifiques comme l'état de santé ou la décision du médecin.
Aucune (un seul groupe de participants) : tous les participants reçoivent le même traitement, aucune répartition n'est nécessaire.

Comment les traitements sont administrés aux participants
Les participants sont répartis en groupes distincts, chaque groupe recevant un traitement différent en même temps. Cela permet de comparer directement l'efficacité de plusieurs traitements.

Autres façons d'administrer les traitements
Groupe unique : tous les participants reçoivent le même traitement.
Affectation croisée : les participants passent d'un traitement à un autre au cours de l'étude.
Plan factoriel : les participants reçoivent des combinaisons de traitements pour évaluer leurs interactions.
Plan séquentiel : les traitements sont administrés successivement selon un ordre prédéterminé, pouvant varier selon la réaction du participant.
Autre type d'attribution : L'attribution des traitements ne suit pas de schéma standard ni de protocole prédéfini.

Comment l'efficacité du traitement est contrôlée
Dans ce type d’étude, aucun participant ne reçoit de placebo. Tous reçoivent soit le traitement expérimental, soit un autre traitement actif, souvent le traitement de référence. Ce modèle permet de comparer les effets de deux interventions réelles, sans inclure de substance inactive.

Autres options possibles
Contrôlée par placebo : un placebo est utilisé pour comparer les effets du traitement expérimental à ceux d'une substance inactive, ce qui permet d'évaluer son efficacité réelle.

Comment la nature du traitement est tenue confidentielle
Dans une étude en ouvert, tous les participants ainsi que les chercheurs savent quel traitement est administré. Ce type de protocole est utilisé lorsqu'il n'est pas nécessaire ou pas possible de masquer les traitements.

Autres méthodes de masquage
Simple aveugle : les participants ignorent le traitement reçu, mais les chercheurs le connaissent.
Double aveugle : ni les participants ni les chercheurs ne savent quel traitement est administré.
Triple aveugle : Les participants, les chercheurs et les personnes qui analysent les résultats ne savent pas quel traitement est administré.
Quadruple aveugle : Les participants, les chercheurs, les personnes qui analysent les résultats et les professionnels de santé en charge du suivi ne savent pas non plus quel traitement est administré.

Éligibilité

Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.
Conditions
Critères
Tout sexeLe sexe biologique des participants éligibles à s'inscrire.
À partir de 18 ansTranche d'âge des participants éligibles à participer.
Volontaires sains non autorisésIndique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.
Conditions
Pathologie
Maladies de la moelle osseuse
Maladie
Maladies Hématologiques
Syndromes myélodysplasiques
Néoplasmes
Processus pathologiques
États précancéreux
Préleucémie
Syndrome
Critères

Inclusion Criteria: * Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High. * Be 18 years of age or older * Have a life expectancy of at least 3 months * Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission * Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory * Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis) * Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal Exclusion Criteria: * Secondary myelodysplastic syndromes (MDS) * Prior treatment with azacitidine; * Prior history of acute myeloid leukemia (AML); * Malignant disease diagnosed within prior 12 months; * Metastatic disease; * Hepatic tumors; * Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months; * Prior transplantation or cytotoxic therapy to treat MDS; * Serious medical illness likely to limit survival to 12 months or less; * Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days; * Active HIV, viral hepatitis type B or C; * Treatment with investigational drugs during prior 30 days; * Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency

Plan de l'étude

Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.
Groupes de traitement
Objectifs de l'étude
2 groupes d'intervention 

sont désignés dans cette étude

Cette étude ne comporte pas de groupe placebo. 

Groupes de traitement
Groupe I
Expérimental
Study Drug plus best supportive care. Treatment with erythropoietin was not permitted

Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m\^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.
Groupe II
Comparateur actif
Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted

Physician Choice was one of three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care
Objectifs de l'étude
Objectifs principaux

Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.

Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.

Count of participants who died during the study
Objectifs secondaires

The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up.

The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death.

Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Investigator determined responses followed IWG criteria for * complete remission(CR): repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia * partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment * stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months.

IWG 2000 Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase or transfusion independent. Minor- 10-20g/L increase or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase. Neutrophil response: Major-\>=100% increase or an absolute increase of \>0.5x10\^9/L. Minor-\>=100% increase and absolute increase of \<0.5x10\^9/L.

The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause.

The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause.

The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit.

Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments.

Centres d'étude

Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.
Cette étude comporte 108 sites
Suspendu
Universita Degli Studi Di SassariSassari, ItalyVoir le site
Suspendu
National Centre of Hematology and Transfusiology, SofiaSofia, Bulgaria
Suspendu
Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of HematologyVarna, Bulgaria
Suspendu
University Multiprofile Hospital for Active Treatment "Sveta Marina"Varna, Bulgaria
Terminé108 Centres d'Étude